The long term goal of this project is to determine the cellular mechanisms of olfaction. This proposal will focus on the initial steps leading to olfactory perception: transduction and adaptation in the olfactory receptor cells. Recent progress on the molecular biology, biochemistry, and electrophysiology of olfactory receptor cells have identified a number of intracellular messengers that may be involved in the transduction of odorous stimuli into an electrophysiological response. Nevertheless, many key questions remain unanswered regarding the importance of each putative messenger and it's role in generating or modulating odorant responses. These questions will be addressed by using patch clamp recordings from solitary receptor cells. First, the properties of the odorant-induced transduction current will be characterized. The currents evoked by all of the putative second messengers will be characterized and compared with the currents evoked by odorants. These data, together with observations on the effects of pharmacologic agents that interfere with the putative transduction mechanisms, will establish the functions of each of the intracellular messengers in olfactory transduction. Adaptation will be studied in a similar manner. A major strength of these experiments will be the use of a mammalian animal model, the rat, which will permit direct comparisons between the electrophysiological data obtained and the growing body of biochemical and molecular genetic data from rodents. An additional strength will be the use, of a novel approach: photolytically activated second messengers and odorants. This project will provide novel data about processes occurring within mammalian olfactory receptor cells, information that can have immediate relevance to human olfaction, as we have shown for induction of olfactory sensitivity in mice. In addition, this work will serve as foundation for relating physiological studies on a variety of species to the physiology and pathology of human olfactory receptor cells.